Exaggerated renal fibrosis in P2X4 receptor-deficient mice following unilateral ureteric obstruction.
Nephrol Dial Transplant
; 29(7): 1350-61, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24574541
ABSTRACT
BACKGROUND:
The ATP-sensitive P2X7 receptor (P2X7R) has been shown to contribute to renal injury in nephrotoxic nephritis, a rodent model of acute glomerulonephritis, and in unilateral ureteric obstruction (UUO), a rodent model of chronic interstitial inflammation and fibrosis. Renal tubular cells, endothelial cells and macrophages also express the closely related P2X4 receptor (P2X4R), which is chromosomally co-located with P2X7R and has 40% homology; it is also pro-inflammatory and has been shown to interact with P2X7R to modulate its pro-apoptotic and pro-inflammatory effects. Therefore, we chose to explore the function of P2X4R in the UUO model of renal injury using knockout mice. We hypothesized that UUO-induced tubulointerstitial damage and fibrosis would also be attenuated in P2X4R(-/-) mice.METHOD:
P2X4R(-/-) and wild-type (WT) mice were subjected to either UUO or sham operation. Kidney samples taken on Days 7 and 14 were evaluated for renal inflammation and fibrosis, and expression of pro-fibrotic factors.RESULTS:
To our surprise, the obstructed kidney in P2X4R(-/-) mice showed more severe renal injury, more collagen deposition (picrosirius red staining, increase of 53%; P < 0.05) and more type I collagen staining (increase of 107%; P < 0.01), as well as increased mRNA for TGF-ß (increase of 102%, P < 0.0005) and CTGF (increase of 157%; P < 0.05) by Day 14, compared with the UUO WT mice.CONCLUSION:
These findings showed that lack of P2X4R expression leads to increased renal fibrosis, and increased expression of TGF-ß and CTGF in the UUO model.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Obstrucción Ureteral
/
Receptores Purinérgicos P2X4
/
Riñón
/
Nefritis Intersticial
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nephrol Dial Transplant
Asunto de la revista:
NEFROLOGIA
/
TRANSPLANTE
Año:
2014
Tipo del documento:
Article
País de afiliación:
Suiza